Study of Novel Regorafenib Compounds Utilizing Pharmacophore Mapping, 3D QSAR, Molecular Docking, and Toxicology Prediction

The most common type of cancer is the aberrant growth of cells that divide unchecked, take over the body, and kill off healthy cells while doing so. Despite the usage of various medicines, concerns over the efficacy, safety, and efficiency of older medications are driving up demand for new therapeutic agents. Pyridine derivatives are common in medicinal chemistry because of their wide range of biological activities. In the current study, molecular docking and silico ADME analysis were conducted to determine the potential inhibitory effect of 20 molecules. To examine the structure-activity connections of these substances, this study uses molecular docking, pharmacophore mapping, 3D quantitative structure-activity relationship (QSAR) modeling, and ADME (absorption, distribution, metabolism, and excretion) prediction. To help identify possible lead drugs, pharmacophore models were created based on important chemical characteristics that cause biological action. When designing inhibitors of receptor-interacting protein kinase 2(RIPK2), the PDB 6ES0 activation loop targeting method is used. Out of the 50 compounds, only five (A, B, C, D, and E) were shown to be present in the in-silico data. Because it has the highest binding affinity score in the binding research of the chemical with the protein (-12.1, −12.5, −12.3, −12.7, 11.9Kcal/mol), compounds A, B, C, D, and E were all submitted to Lipinski's rule of five. Because of their strong inhibitory action, pyridine derivatives and their structure are also thoroughly covered in this work for their use as anticancer drugs. These chemicals' potential for bioactivity and possible drug-like properties make them strong candidates for more experimental research.